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Registerextent of accumulation [NCA / SHAM]
Dear Martin,
Sorry, I once again failed to explain my question. You mentioned "accumulation in steady state conditions"; this challenged my walnut-sized brain when I read it as I generally understand steady state as the state where accumulation is absent.
Re. Q1: I think the equation is to be used mainly in case you have reason to expect a monophasic elimination of first order. Hence, applying it to a system with two elimination constants could be disputable. However, using the terminal constant for the purpose would be the conservative approach in a regulators view, I expect. Simulations might help you a good piece of the way.
EM.
❝ Accumulation (e.g. higher AUC after repeated than after first administration) occurs when the dosing interval is "too short" with respect to the half-life of the compound investigated. On the other hand, an increase in drug exposure after repeated dosing may be due to damage to the eliminating organs and subsequent reduction in clearance which may indicate a safety concern.
Sorry, I once again failed to explain my question. You mentioned "accumulation in steady state conditions"; this challenged my walnut-sized brain when I read it as I generally understand steady state as the state where accumulation is absent.
Re. Q1: I think the equation is to be used mainly in case you have reason to expect a monophasic elimination of first order. Hence, applying it to a system with two elimination constants could be disputable. However, using the terminal constant for the purpose would be the conservative approach in a regulators view, I expect. Simulations might help you a good piece of the way.
EM.
Complete thread:
- extent of accumulation martin 2010-01-13 13:38 [NCA / SHAM]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- extent of accumulation ElMaestro 2010-01-13 16:15
- extent of accumulation martin 2010-01-13 17:45
- Too short tau? Helmut 2010-01-13 19:14
- Too short tau? martin 2010-01-13 19:45
- Too short tau? Helmut 2010-01-13 20:02
- Too short tau? martin 2010-01-13 19:45
- extent of accumulationElMaestro 2010-01-13 20:47
- Too short tau? Helmut 2010-01-13 19:14
- extent of accumulation martin 2010-01-13 17:45
- extent of accumulation Helmut 2010-01-13 18:16
- principle of superposition martin 2010-01-13 19:14
- principle of superposition Helmut 2010-01-13 19:34
- principle of superposition martin 2010-01-13 19:14
- extent of accumulation ElMaestro 2010-01-13 16:15
Ing. Helmut Schütz